SCI 발표논문
전체 4,588편
- 582005
제1저자 Moon MK · 교신저자 박경수
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Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with Type 2 diabetes mellitus and obesity in the Korean population.Diabet Med. 2005;22(9):1161-6.
PubMed IF 3.3 내분비대사내과Abstract
AIMS We examined whether the common polymorphisms of the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or obesity in the Korean population.
METHODS We genotyped two common PPARgamma polymorphisms (Pro12Ala and 161C > T) and examined their association with the clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291 non-diabetic control subjects.
RESULTS The 12Ala allele was less frequent in the Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs. 0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the non-diabetic controls, those with the T allele had lower BMI and fasting serum triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9 vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P = 0.03, respectively). The 12Ala-161T haplotype was associated with a decreased risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7 +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02, respectively).
CONCLUSIONS The PPARgamma 12Ala allele was associated with a reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated with lower BMI and fasting serum TG concentrations in the Korean subjects. The subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes.
- 572005
제1저자 조상헌 · 교신저자 김윤근
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Association between bronchodilating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene.Clin Exp Allergy. 2005;35(9):1162-7.
PubMed IF 5 알레르기내과Abstract
BACKGROUND With beta-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that beta(2)-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation.
OBJECTIVE The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting beta-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27).
METHODS Two hundred and nine children with reduction in forced expiratory volume in 1 s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5 min after the inhalation of 200 mug of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms.
RESULTS The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone.
CONCLUSION Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting beta-agonists.
- 562005
제1저자 김상완 · 교신저자 김성연,신찬수
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Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells.Bone. 2005;37(3):359-69.
PubMed IF 3.9 내분비대사내과Abstract
Ghrelin is a 28-amino-acid peptide identified in the stomach as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates the release of growth hormone at the hypothalamus and pituitary level. Although GHS-Rs are expressed in a variety of peripheral tissues, little is known about its effect on bone independent of GH/IGF-1 axis. This study was undertaken to investigate whether ghrelin exerts a direct effect on osteoblasts. We identified mRNA and protein expression of GHS-R in primary osteoblasts as well as a number of osteoblastic cell lines, including MC3T3-E1, ROS 17/2.8, UMR-106, MG63, and SaOS2 cells. Treatment of ghrelin (10(-11) to 10(-7) M) to MC3T3-E1 cells showed dose-dependent stimulation of proliferation, which was abrogated by treatment with [d-Lys]-GHRP-6 (10(-3) M), a selective antagonist of the ghrelin receptor. Ghrelin activated ERK1/2 MAPK and pretreatment with MAPK kinase inhibitors, PD98059 attenuated the ghrelin-induced cell proliferation. Ghrelin also inhibited TNFalpha-induced apoptosis and suppressed caspase-3 activation that occurs in response to TNFalpha as well as during in vitro differentiation process. Moreover, ghrelin treatment enhanced in vitro osteoblast differentiation as evidenced by matrix mineralization, alkaline phosphatase activity, and osteoblast-specific gene expression. These results suggest that ghrelin promotes proliferation and differentiation and inhibits apoptosis of osteoblasts.
- 552005
제1저자 김나영 · 교신저자 송인성
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Seroconversion of Helicobacter pylori in Korean male employees.Scand J Gastroenterol. 2005;40(9):1021-7.
PubMed IF 1.8 소화기내과Abstract
OBJECTIVE Helicobacter pylori infections are acquired primarily during childhood, but also occur in adults. As no published estimates are available on the seroconversion rate of H. pylori in the Korean population, the purpose of this study was to evaluate the incidence and prevalence of H. pylori infection in male Korean employees.
MATERIAL AND METHODS Levels of anti-H. pylori IgG were measured by ELISA, and gastroscopic findings were checked in 588 employees of the Subway Corporation (aged 40-60 years, male) in 1997, 1998, 1999, 2000, and 2003. Questionnaire responses concerning socio-economic state, education level, and type of job were analyzed versus serologic test results.
RESULTS Out of the 588 subjects, 455 (77.4%) were positive for anti-H. pylori IgG. Multivariate analysis showed that abnormal gastroscopic findings, especially duodenal ulcers, were more frequent in the H. pylori-positive group (17.6) than in the initially H. pylori-negative group (9.0%) (OR: 1.71, 95% CI: 1.07-2.81). Among the multiple questionnaires, only the proportion of white-collar workers was significant; that is, it was lower in the H. pylori-positive group (44/6) than in the initial H. pylori-negative group (57.9%) (OR: 0.62, 95% CI: 0.41-0.92). Seventeen of 133 subjects (12.8%) who were initially seronegative underwent seroconversion during a 6-year follow-up period, a seroconversion rate of 2.13%/annum.
CONCLUSIONS The seroprevalence of H. pylori infection in this study group was 77.4% and duodenal ulcer was more frequent in H. pylori-positive subjects, thus confirming the relationship between H. pylori infection and duodenal ulcer. Seroconversion of H. pylori infection in the Korean male employees was determined to be 2.13% per year, suggesting that new infections occur continuously even during late adulthood.
- 542005
제1저자 오도연 · 교신저자 허대석
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Management of gastric lymphoma with chemotherapy alone.Leuk Lymphoma. 2005;46(9):1329-35.
PubMed IF 2.1 혈액종양내과Abstract
PURPOSE The optimal therapy for gastric lymphoma except MALToma has not yet been established. This study was undertaken to investigate whether gastric lymphoma can be managed effectively and safely with chemotherapy alone.
PATIENTS AND METHODS A total of 58 patients (median age 56 years) with newly diagnosed gastric lymphoma between 1989--2001 at Seoul National University Hospital and who were initially managed with chemotherapy alone were evaluated. MALToma was excluded from the pathologic review.
RESULTS All patients received initially anthracycline-containing chemotherapy. ECOG performance scale 0--1 was 88% and B symptoms were present in 41.4%. Diffuse large B cell type was the most common (74.1%). Stage IE, II1E accounted for 51.7% and II2E, IIIE, IV for 48.3%. The international prognostic index (IPI) of risk was low in 39.7%, low-intermediate in 22.4%, high-intermediate in 15.5% and high in 22.4%. The complete response rate after first-line chemotherapy was 71.4% and the partial response rate was 12.2%. (overall response rate: 83.6%). Among patients who did not reach the complete response, a further complete response was achieved by second-line chemotherapy including etoposide-based regimen. Ultimately, the maximum complete response rate by chemotherapy was 83.7% (92% in stage IE, II1E, 75% in stage II2E, IIIE, IV). Median overall survival was 47.4 months (84.7 months in stage IE, II1E, 32.5 months in stage II2E, IIIE, IV) and the 5-year survival rate was 46%. Bleeding as a complication occurred in 3 of 58 patients (5.6%) and these cases were controlled by embolization or conservative management. No perforation episode occurred and surgical intervention due to complication was not necessary. Organ preservation was possible in 57 of 58 patients (98%). The one gastrectomy was performed due to a partial clinical response to chemotherapy but the specimen showed pathologic CR. Multivariate analysis revealed that only IPI had a significant influence on survival.
CONCLUSIONS Gastric lymphoma except MALToma can be managed effectively and safely with chemotherapy alone.
- 532005
제1저자 김형관 · 교신저자 김용진
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Impact of the maze operation combined with left-sided valve surgery on the change in tricuspid regurgitation over time.Circulation. 2005;112(9 Suppl):I14-9.
PubMed IF 41.3 순환기내과Abstract
BACKGROUND Atrial fibrillation (AF) has been reported to be a predisposing factor for the progression of TR in patients with previous mitral or combined mitral/aortic valve surgery. We hypothesized that the maze operation (MAZE) can prevent the progression of tricuspid regurgitation (TR) in these patients.
METHODS AND RESULTS We analyzed 170 patients (age, 45.5+/-10.9 years) who had undergone mitral or combined mitral/aortic valve surgery. On the basis of preoperative rhythm, patients were divided into 3 groups; GrI was composed of 44 patients with sinus rhythm, GrII of 48 who had undergone MAZE, and GrIII of 78 with AF who had not undergone MAZE. Echocardiographic examinations were performed before, immediately after, and 92.2+/-17.2 (range, 50 to 131) months after surgery. Preoperative and immediate postoperative clinical and echocardiographic parameters were similar among the groups. Insignificant TR at the immediate postoperative examination worsened with time in 7.3% of GrI (3 of 41), 12.8% of GrII (6 of 47), and 38.8% of GrIII (26 of 67) patients at the final examination (P=0.63 for GrI versus GrII, P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII). The incidence of significant TR at the final echocardiographic examination was higher in GrIII (39.7%) compared with GrI (9.1%) and GrII (14.6%) (P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII), whereas GrI and GrII did not show any difference (P=0.63). By multivariate analysis, the only factor identified to prevent TR progression was the group factor (GrI and GrII versus GrIII, P=0.002 and P=0.005, respectively). In a subgroup analysis of GrII according to the presence or absence of atrial mechanical activity, the absence of atrial mechanical activity was identified as an independent parameter for the progression of TR (P=0.001).
CONCLUSIONS AF predisposes patients undergoing mitral valve surgery to the progression of TR, which can be prevented by MAZE. This additional benefit of MAZE is largely dependent on the restoration and maintenance of atrial mechanical function.
- 522005
제1저자 구본권 · 교신저자 오병희
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Physiologic assessment of jailed side branch lesions using fractional flow reserve.J Am Coll Cardiol. 2005;46(4):633-7.
PubMed IF 22.3 순환기내과Abstract
OBJECTIVES This study was performed to evaluate the feasibility of the physiologic assessment of jailed side branches using fractional flow reserve (FFR) and to compare the measured FFR with the stenosis severity assessed by quantitative coronary angiography (QCA).
BACKGROUND It is not well-known which side branches should be treated after stent implantation at main branches and how to assess the functional significance of these lesions.
METHODS Ninety-seven jailed side branch lesions (vessel size > 2.0 mm, percent stenosis > 50% by visual estimation) after stent implantation at main branches were consecutively enrolled. The FFR was measured using a pressure wire at 5 mm distal and proximal to the ostial lesion of the jailed side branch.
RESULTS The FFR measurement was successful in 94 lesions. Mean FFRs were 0.94 +/- 0.04 and 0.85 +/- 0.11 at the main branches and jailed side branches, respectively. There was a negative correlation between the percent stenosis and FFR (r = -0.41, p < 0.001). However, no lesion with < 75% stenosis had FFR < 0.75. Among 73 lesions with > or = 75% stenosis, only 20 lesions were functionally significant.
CONCLUSIONS The FFR measurement in jailed side branch lesions is both safe and feasible. Quantitative coronary angiography is unreliable in the assessment of the functional severity of jailed side branch lesions, and measurement of FFR suggests that most of these lesions do not have functional significance.
- 512005
제1저자 Byrd RP · 교신저자 이춘택
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Pneumothorax following transthoracic fine-needle aspiration of the lung.Chest. 2005;128(2):1071; author reply 1071-2.
- 502005
제1저자 임석아 · 교신저자 김성배
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Docetaxel plus epirubicin as first-line chemotherapy in MBC (KCSG 01-10-05): phase II trial and the predictive values of circulating HER2 extracellular domain and vascular endothelial growth factor.Oncol Rep. 2005;14(2):481-7.
PubMed IF 4.7 혈액종양내과Abstract
The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer (MBC). We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospective assessment of the predictive values of circulating HER2 extracellular domain (ECD) and vascular endothelial growth factor (VEGF). Docetaxel 75 mg/m(2) and epirubicin 75 mg/m(2) were given intravenously every 3 weeks. Prophylactic G-CSF was not used. Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay. Forty MBC patients were enrolled, and 39 patients were evaluable for toxicities and 38 for response. Complete response was observed in 3 (7.9%) patients, partial response in 20 (52.6%) (overall response rate 60.5%), stable disease in 11 (28.9%) and disease progression in 4 (10.5%). After a median follow-up of 22.5 months, the median duration of response was 28 weeks, median time to disease progression was 32 weeks, and median survival was 15.8 months. Two-hundred and fifteen cycles of treatment were administered (median, 6 cycles per patient). Grade 3 and 4 neutropenia were observed during 24 (11.2%) and 74 (35%) cycles respectively, and grade 3 or 4 febrile neutropenia in 24 (11.2%) cycles. Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration (p<0.005) and shorter time to progression (p<0.005). However, elevated VEGF levels were not found to be correlated with response rate or survival. We concluded that the docetaxel and epirubicin combination is an effective first-line treatment in MBC patients and that elevated serum HER2 ECD levels, but not circulating VEGF levels, predict a poor outcome.
- 492005
제1저자 구본권 · 교신저자 김철호
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Intracoronary continuous adenosine infusion.Circ J. 2005;69(8):908-12.
PubMed IF 5.8 순환기내과Abstract
BACKGROUND Various methods are used to induce maximal hyperemia for physiologic studies, but the feasibility and efficacy of continuous intracoronary (IC) infusion of adenosine for measurement of fractional flow reserve (FFR) has not been well-defined.
METHODS AND RESULTS Patients with intermediate coronary artery stenosis were consecutively enrolled. In the phase I study, FFR was measured after 3 dosages of IC adenosine infusion (180, 240 and 300 microg/min) in 30 patients. The phase II study was performed to compare the hyperemic efficacy of IC infusion (240 microg/min) with IC bolus injection (40, 80 microg) and intravenous (IV) infusion (140 microg x kg (-1) x min(-1)) of adenosine in 20 patients. In the phase I study, no significant differences in FFR were observed with the 3 different doses of IC infusion (p = 0.06). In the phase II study, FFR after an IC bolus injection (0.83+/-0.06) was significantly higher than with IV (0.79+/-0.07) or IC (0.78+/-0.09) infusion (p < 0.01). However, no difference in FFR was observed for IC and IV infusions.
CONCLUSION IC infusion of adenosine seems to be a safe and effective method of inducing maximal hyperemia for FFR measurement.
- 482005
제1저자 김대영 · 교신저자 허대석
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Efficacy of platinum-based chemotherapy after cranial radiation in patients with brain metastasis from non-small cell lung cancer.Oncol Rep. 2005;14(1):207-11.
PubMed IF 4.7 혈액종양내과Abstract
This study was conducted to assess the efficacy of systemic chemotherapy in patients with brain metastasis from non-small cell lung cancer. Sixty-three consecutive patients who were diagnosed as having non-small cell lung cancer (NSCLC) with synchronous brain metastasis (BM) and had not been previously treated were included in this study. After cranial radiation therapy (RT), all patients in 'the chemotherapy arm' (CTX) were treated with platinum-based combination chemotherapy, and best supportive care was selected for patients in 'the no-chemotherapy arm' (no-CTX). Thirty-one of the 63 patients received systemic chemotherapy. The median age of all patients was 55 years. The performance status of all patients was ECOG grade 1-2. Twenty-two patients had a solitary brain metastasis, 37 patients had more than two masses, and 38 patients had extracranial metastatic lesions. In the CTX arm, a paclitaxel-based combination chemotherapy was administered in 38.7%, gemcitabine-based in 25.8%, and vinorelbine-based in 25.8% as the first-line chemotherapy. Seventeen patients were treated with a second-line chemotherapy, and paclitaxel plus gemcitabine was used in 8 patients. For the first-line and second-line chemotherapies, extracranial overall responses were 36 and 35%, the median response durations were 29.1 weeks (range: 9.1-58.1 weeks) and 30.4 weeks (range: 19.4-44.0 weeks), respectively. 'Progression of the extracranial lesion' (58.1%) was more frequent than an 'aggravation of neurologic status' (19.4%) for the pattern of treatment failure in the first-line chemotherapy. The causes of failure were identical in the second-line chemotherapy. The median survival of the CTX arm was longer than that of the no-CTX arm (58.1 vs. 19.0 weeks, p<0.001). Toxicity in the CTX arm was tolerable. The systemic chemotherapy showed an effectiveness to increase the survival of patients with BM from NSCLC, and extracranial progression was the main cause of chemotherapeutic failure, although consideration for non-randomized methods should be made in this study.
- 472005
제1저자 임수 · 교신저자 조성일
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Changes in the characteristics of metabolic syndrome in Korea over the period 1998-2001 as determined by Korean National Health and Nutrition Examination Surveys.Diabetes Care. 2005;28(7):1810-2.
- 462005
제1저자 이경희 · 교신저자 유철규
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Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the IkappaB/NF-kappaB cascade by facilitating IkappaB kinase renaturation and blocking its further denaturation.Exp Cell Res. 2005;307(1):276-84.
PubMed IF 3.5 호흡기내과Abstract
Heat shock (HS) treatment has been previously shown to suppress the IkappaB/nuclear factor-kappaB (NF-kappaB) cascade by denaturing, and thus inactivating IkappaB kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the IkappaB/NF-kappaB cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-alpha-induced activation of the IkappaB/NF-kappaB pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-alpha-induced activation of the IkappaB/NF-kappaB pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayed TNF-alpha-induced IkappaBalpha degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the IkappaBalpha stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the IkappaB/NF-kappaB cascade by facilitating the renaturation of IKK and blocking its further denaturation.
- 452005
제1저자 오도연 · 교신저자 허대석
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Docetaxel + 5-fluorouracil + cisplatin 3-day combination chemotherapy as a first-line treatment in patients with unresectable gastric cancer.Jpn J Clin Oncol. 2005;35(7):380-5.
PubMed IF 2.5 혈액종양내과Abstract
BACKGROUND Our objective was to verify the efficacy and safety of "docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy as a first-line treatment in patients with unresectable gastric cancer.
METHODS Between January and November 2002, we enrolled 43 patients [males 31; median age 55 years (range 24-74)] with inoperable gastric cancer who had not been seen previously in Seoul National University Hospital. The regimen used was docetaxel 70 mg/m(2) on day 1, cisplatin 40 mg/m(2) on days 2 and 3, and 5-fluorouracil 1200 mg/m(2) over 10 h on days 1-3, every 3 weeks.
RESULTS A total of 168 cycles were administered. Mean cycle number per patient was 3.9. The administered dose intensity of docetaxel was 21.23 mg/m(2)/week, 5-FU 1092.14 mg/m(2)/week and cisplatin 23.82 mg/m(2)/week, which corresponded to 91.1, 91.0 and 89.5% of planned doses. Of the 43 patients, response evaluation was possible in 40 and, of these patients, 17 (42.5%) achieved a partial response, 13 (32.5%) stable disease, and 10 patients (25%) showed progressive disease. The median time to progression was 5.6 months [95% confidence interval (CI) 4.6-6.6 months]. Median overall survival was 9.0 months. (95% CI 4.8-13.2 months). Leukopenia occurred during 21.4% of cycles (36 of 168 cycles); 14.3% grade 1, 5.3% grade 2 and 1.8% grade 3. Anemia occurred in 16.7% (28 of 168 cycles); 11.3% grade 1, 4.8% grade 2 and 0.6% grade 3. Thrombocytopenia was not observed. Diarrhea, stomatitis and hypersensitivity occurred in 4.7% (two out of 43 patients), respectively. Neutropenic fever occurred in two patients (4.7%) and myalgia in three (7.0%).
CONCLUSION "Docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy is an active and tolerable regimen as a first-line treatment in patients with unresectable gastric cancer.
- 442005
제1저자 Kim JH · 교신저자 박경수
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Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population.Diabetologia. 2005;48(7):1323-30.
PubMed IF 10.4 내분비대사내과Abstract
AIMS/HYPOTHESIS Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) is a transcriptional coactivator implicated in insulin release by beta cells and in insulin resistance. Therefore, genetic variation of PPARGC1A could be implicated in the onset of type 2 diabetes. In this study, we examined whether the PPARGC1A gene locus is associated with type 2 diabetes mellitus. We also investigated its association with clinical and metabolic parameters in healthy and diabetic subjects.
METHODS After sequencing exons and their boundaries of the PPARGC1A gene, including the promoter region ( approximately 1.5 kb), we genotyped eight common single nucleotide polymorphisms (SNPs) in an association study comprising 762 unrelated patients with type 2 diabetes and 303 non-diabetic control patients. We divided the patients with type 2 diabetes into quartiles or three groups according to age at diagnosis of type 2 diabetes (early-onset: <40 years of age, average-onset: 40< or = <60 years, and late-onset: > or =60 years).
RESULTS There was no strong association between SNPs or haplotypes of PPARGC1A and type 2 diabetes. However, the SNPs of g.-1789G>A and g.-1437C>T were associated with the age at diagnosis of type 2 diabetes (p=0.042 and p=0.032, respectively). In addition, the promoter SNPs of g.-1789G>A and g.-1437C>T and the haplotypes ht2 (-1789A and -1437T) were significantly associated with early-onset type 2 diabetes (p=0.002, p=0.001 and p=0.001, respectively).
CONCLUSIONS/INTERPRETATION Our results suggest that PPARGC1A promoter polymorphisms are associated with age at diagnosis of type 2 diabetes and early-onset type 2 diabetes in the Korean population.
- 432005
제1저자 김윤준 · 교신저자 홍선포
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Population genotyping of hepatitis C virus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of short DNA fragments.Clin Chem. 2005;51(7):1123-31.
PubMed IF 8.3 소화기내과Abstract
BACKGROUND Identifying hepatitis C virus (HCV) genotypes has become increasingly important for determining clinical course and the outcome of antiviral therapy. Here we describe the development of restriction fragment mass polymorphism (RFMP) analysis, a novel matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay suitable for high-throughput, sensitive, specific genotyping of multiple HCV species.
METHODS The assay is based on PCR amplification and mass measurement of oligonucleotides containing genotype-specific motifs in the 5' untranslated region, into which a type IIS restriction endonuclease recognition was introduced by PCR amplification. Enzymatic cleavage of the products led to excision of multiple oligonucleotide fragments representing variable regions whose masses were determined by MALDI-TOF MS.
RESULTS The RFMP assay identified viral genotypes present at concentrations as low as 0.5% and reliably determined their relative abundance. When sera from 318 patients were analyzed, the RFMP assay exhibited 100% concordance with results obtained by clonal sequencing and identified mixed-genotype infections in 22% of the samples, in addition to several subtype variants.
CONCLUSIONS The RFMP assay has practical advantages over existing methods, including better quantitative detection of mixed populations and detection of genotype variants without need for population-based cloning, enabling reliable viral genotyping in laboratories and efficient study of the relationship between viral genotypes and clinical outcome.
- 422005
제1저자 송영욱 · 교신저자 박명희
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Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean patients.Hum Immunol. 2005;66(7):810-7.
PubMed IF 2.1 류마티스내과Abstract
We sought to determine whether transporter associated with antigen processing (TAP) gene polymorphism is associated with susceptibility to systemic sclerosis (SSc). TAP1 and TAP2 gene polymorphisms were analyzed in 61 Korean patients with SSc and 100 ethnically matched healthy Koreans by polymerase chain reaction-restriction fragment length polymorphism. Human leukocyte antigen (HLA)-DRB1 genotyping data of the patients from our previous study was used for the assessment of independent role of TAP genes to SSc susceptibility. Patients were stratified according to anti-topoisomerase I (anti-topo I) antibody status and clinical subsets of diffuse and limited cutaneous SSc (dcSSc and lcSSc). TAP1 and TAP2 gene polymorphisms were associated with different subsets of SSc: TAP1*A/A genotype with anti-topo I-positive dcSSc (p = 0.01, p corrected = 0.04), TAP2*A1/C genotype with anti-topo I-positive lcSSc (p < 0.05), TAP2*Bky2 and *C alleles with anti-topo I-negative dcSSc (both p < 0.05), and TAP2*B/E genotype with anti-topo I-negative lcSSc (p = 0.004). Although TAP gene associations were generally weak, some associations (TAP2*A1/C, TAP2*C, and TAP2*B/E) with different subsets of SSc were independent of HLA-DR associations, revealing even stronger associations (TAP2*A1/C and TAP2*C) among individuals not possessing the risk HLA-DR alleles. These results suggest the possible role of TAP gene polymorphisms in the genetic susceptibility to SSc.
- 412005
제1저자 최의근 · 교신저자 김효수
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Novel index of coronary collateral development as a useful predictor of clinical outcome in type 2 diabetic patients with coronary artery disease.Circ J. 2005;69(7):786-92.
PubMed IF 5.8 순환기내과Abstract
BACKGROUND There is a paucity of information regarding the impact of the coronary collaterals on prognosis in type 2 diabetic (T2DM) patients. We developed a novel index, which considers not only the degree of collateral circulation but also the stimulus of collateral development, and investigated its prognostic value in T2DM patients with coronary artery disease (CAD).
METHODS AND RESULTS One hundred and ninety four consecutive T2DM patients were analyzed and followed for an average of 30 months. We measured the diameter stenosis (DS; %), corrected TIMI frame count (CTFC) and Rentrop score at 3 major epicardial coronary arteries. The collateral development (CD) score was calculated by: (Sigma Rentrop score +1)/Sigma [DS (%) x CTFC] x1,000. During the follow-up, acute cardiovascular events occurred in 49 patients. By multivariate analysis, the CD score was an independent predictor of adverse events not only in the total population (p<0.001), but in all 3 subgroups (p=0.020 for coronary artery bypass grafting, p=0.030 for percutaneous transluminal coronary angioplasty (PTCA) and p=0.003 for the medical group). Furthermore, patients in the tertile with the highest CD score showed improved survival by Kaplan-Meier analysis in the total population, the PTCA and the medical group.
CONCLUSIONS The CD score, a novel index of collateral development, may be a useful predictor of clinical outcome in T2DM patients with CAD.
- 402005
제1저자 강영애 · 교신저자 임재준
, , , , , ,
Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country.JAMA. 2005;293(22):2756-61.
PubMed IF 65.4 호흡기내과Abstract
CONTEXT A recently developed whole-blood interferon gamma (IFN-gamma) assay based on stimulation with the Mycobacterium tuberculosis-specific antigens early secreted antigenic target 6 and culture filtrate protein 10 shows promise for the diagnosis of latent tuberculosis (TB) infection.
OBJECTIVE To compare the tuberculin skin test (TST) and the whole-blood IFN-gamma assay in the diagnosis of latent TB infection according to the intensity of exposure.
DESIGN AND SETTING A prospective comparison between the whole-blood IFN-gamma assay and the TST using a 2-TU dose of purified protein derivative RT23 in a population with intermediate TB burden was conducted sequentially between February 1, 2004, and February 28, 2005, in a Korean tertiary referral hospital.
PARTICIPANTS Of 273 participants, 220 (95.7%) had received BCG vaccine. Participants were grouped according to their risk of infection: group 1, no identifiable risk of M tuberculosis infection (n = 99); group 2, recent casual contacts (n = 72); group 3, recent close contacts (n = 48); group 4, bacteriologically or pathologically confirmed TB patients (n = 54).
MAIN OUTCOME MEASURES Levels of agreement between the TST and the IFN-gamma assay and the likelihood of infection in the various groups.
RESULTS For the TST with a 10-mm induration cutoff, the positive response rate in group 1 was 51%; group 2, 60%; group 3, 71%, and group 4, 78%. For the IFN-gamma assay, the positive response rate in group 1 was 4%; group 2, 10%; group 3, 44%; and group 4, 81%. The overall agreement between the TST and the IFN-gamma assay in healthy volunteers was kappa = 0.16. The odds of a positive test result per unit increase in exposure across the 4 groups increased by a factor of 5.31 (95% confidence interval [CI], 3.62-7.79) for the IFN-gamma assay and by a factor of 1.52 (95% CI, 1.20-1.91) for the TST (P<.001). Using a 15-mm induration cutoff for the TST did not make a substantial difference to the test results.
CONCLUSION The IFN-gamma assay is a better indicator of the risk of M tuberculosis infection than TST in a BCG-vaccinated population.
- 392005
제1저자 신기철 · 교신저자 송영욱
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Reversible posterior leukoencephalopathy syndrome in systemic lupus erythematosus with thrombocytopenia treated with cyclosporine.J Clin Rheumatol. 2005;11(3):164-6.
PubMed IF 1.9 류마티스내과Abstract
Thrombocytopenia is one of the common manifestations of systemic lupus erythematosus (SLE). Its treatment consists of corticosteroids and/or other immunosuppressive drug such as azathioprine, vincristine, cyclosporine, and mycophenolate mofetil. Common adverse reactions of immunosuppressive treatment are infections, hematologic and liver function abnormalities, but neurologic complications may also be seen. Reversible posterior leukoencephalopathy syndrome (RPLS) is a syndrome manifested by headache, nausea, vomiting, seizures, cortical blindness, and visual disturbances. Neuroimaging shows bilateral subcortical and cortical edema with prominent posterior distribution. Moreover, treatment with immunosuppressive drugs such as cyclosporine, cisplatin, tacrolimus, and interferon-alpha can induce a condition resembling RPLS. We report a case of a young woman with SLE and thrombocytopenia, who developed severe perspiration, headache, and seizure after receiving cyclosporine. A brain magnetic resonance image showed multiple high signal intensities on T2-weighted images predominantly located at the parietooccipital lobe. The patient recovered completely clinically and radiologically after discontinuing cyclosporine.
- 382005
제1저자 김주영 · 교신저자 김병국
, , , , , , , ,
Radioprotective effects of various cytokines in peripheral blood mononuclear cells and C3H mice.Oncol Rep. 2005;13(6):1177-83.
PubMed IF 4.7 혈액종양내과Abstract
The purpose of this study was to investigate the radioprotective effect of HGFs (GM-CSF, IL-3 and SCF) in irradiated human peripheral blood mononuclear cells (PBMCs) in vitro, and the survival effect of lethally irradiated C3H mice in vivo. The irradiation of human PBMCs using a (137)Cs irradiator showed a dose-dependent inhibition of cell growth up to a dose of 5 Gy. This cell growth inhibition induced apoptosis, which was associated with the down-regulation of Bcl-2, up-regulation of Bax, depolarization of mitochondrial transmembrane potential (Delta psi m), and caspase-3 and -9 activation. Following gamma-irradiation at 2 Gy, IL-3 (10 ng/ml) alone or combined with SCF (50 ng/ml) reduced the apoptotic portion of human PBMCs by 15 and 20% of the cell population, respectively, showing no activation of caspase-3 compared to the control group. To examine the in vivo effect of gamma-irradiation and cytokines, we investigated the survival rate and recovery of peripheral blood cells in C3H mice. C3H mice subjected to total body irradiation (TBI) at a dose of 7 Gy (lethal dose 83% at 30 days) showed time-dependent decreases in RBC, WBC and platelet counts, with the nadir occurring at 12 to 15 days. However, treatment with recombinant murine (rm) SCF (2 microg/day s.c.), rmIL-3 (2 microg/day s.c.), or rmG-CSF (2.5 microg/day s.c.) 24 h before and after irradiation did not promote hematologic recovery or survival in the lethally irradiated C3H mice. These findings indicate that the combined treatment of IL-3 and SCF prevents the apoptosis induced in PBMCs by gamma-irradiation in vitro, but it does not afford any in vivo radioprotective effect in lethally irradiated C3H mice.
- 372005
제1저자 조현재 · 교신저자 김효수
, , , , , , , , , , ,
Regulation of endothelial cell and endothelial progenitor cell survival and vasculogenesis by integrin-linked kinase.Arterioscler Thromb Vasc Biol. 2005;25(6):1154-60.
PubMed IF 8.8 순환기내과Abstract
OBJECTIVE New vessel formation is a dynamic process of attachment, detachment, and reattachment of endothelial cells (ECs) and endothelial progenitor cells (EPCs) with each other and with the extracellular matrix (ECM). Integrin-linked kinase (ILK) plays a pivotal role in ECM-mediated signaling. Therefore, we investigated the role of ILK in ECs and EPCs during neovascularization.
METHODS AND RESULTS In human umbilical cord vein ECs and EPCs, endogenous ILK expression, along with subsequent cell survival signals phospho-Akt and phospho-glycogen synthase kinase 3beta, was reduced after anchorage or nutrient deprivation. Even brief anchorage deprivation resulted in retarded capillary tube formation by ECs. Adenoviral ILK gene transfer in ECs and EPCs reversed the decrease in cell survival signals after anchorage or nutrient deprivation, leading to enhanced survival, reduced apoptosis, and significantly accelerated the functional recovery after reattachment. And ILK overexpressing EPCs significantly improved blood flow recovery and prevented limb loss in nude mice hindlimb ischemia model. Furthermore, the efficacy of systemic delivery was equivalent to local injection of ILK-EPCs.
CONCLUSIONS ILK overexpression protects ECs and EPCs from anchorage- or nutrient-deprived stress and enhances neovascularization, suggesting that ILK is an optimal target gene for genetically modified cell-based therapy. Neovascularization is a dynamic process of detachment and reattachment of ECs and EPCs. Endogenous ILK expression was decreased in various stress conditions, and the gene transfer of ILK protected ECs and EPCs from temporary anchorage or nutrient deprivation. Furthermore, ILK gene transfer in EPCs significantly enhanced neovascularization in vivo.
- 362005
제1저자 Chung SS · 교신저자 박경수
, , , , ,
Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site.Diabetologia. 2005;48(6):1150-8.
PubMed IF 10.4 내분비대사내과Abstract
AIMS/HYPOTHESIS Resistin is an adipokine that might link obesity and insulin resistance. A common polymorphism of the human resistin gene, -420C >G, is a major determinant of plasma resistin concentrations as well as resistin mRNA expression in human adipose tissue. In this study, we investigated the regulatory mechanism by which this polymorphism affects resistin expression.
METHODS Electrophoretic mobility shift assay was performed to identify the transcription factors binding to the -420G region. Transient transfection and reporter assay were used to measure promoter activities of the resistin gene. The binding ability of stimulatory protein 1 (Sp1) in response to adipocyte differentiation or high glucose concentrations was also measured.
RESULTS Sp1 and stimulatory protein 3 (Sp3) specifically bound to the region around -420G of the human resistin gene. Overexpression of Sp1 increased the promoter activity regardless of -420 genotypes, while the promoter activity of the -420G construct was two-fold higher than that of the -420C construct. In contrast, overexpression of Sp3 scarcely increased the promoter activity. The binding ability of Sp1 to the -420G region was increased in response to adipocyte differentiation. Mithramycin A, an inhibitor of DNA binding of Sp1, reduced the effect of high glucose on transcription induction of the resistin gene in adipocytes.
CONCLUSIONS/INTERPRETATION These results suggest that Sp1 is an important factor regulating transcription of human resistin gene. A common polymorphism of the human resistin promoter, -420C >G, is critical for the binding of Sp1 and modulates the transcriptional activity of the resistin gene by changing the binding ability of Sp1. In addition, Sp1 may be involved in the increase of resistin expression by hyperglycaemia.
- 352005
제1저자 김지현 · 교신저자 방영주
, , , , , , , , , ,
Cytotoxic effects of pemetrexed in gastric cancer cells.Cancer Sci. 2005;96(6):365-71.
PubMed IF 4.9 혈액종양내과Abstract
Pemetrexed is a newly developed multitargeted antifolate with promising clinical activity in many solid tumors including gastric cancer. The aim of the present study was to evaluate the cytotoxicity of pemetrexed and its mode of interaction with cisplatin in gastric cancer cell lines, and to identify genes associated with sensitivity to pemetrexed. The cytotoxic activity of pemetrexed was assessed by tetrazolium-based colorimetric assay (MTT assay) and the interaction between pemetrexed and cisplatin was evaluated by the isobologram method. Western immunoblotting and real time RT-PCR analysis of thymidylate synthase (TS), folylpoly-gamma-glutamate synthetase (FPGS) and reduced folate carrier (RFC1) were performed in order to determine whether sensitivity to pemetrexed would be predictable by protein or mRNA expression levels. Pemetrexed was more cytotoxic than 5-fluorouracil, with IC50 between 17 and 310 nM in most of the gastric cancer cell lines examined and the pemetrexed/cisplatin combination resulted in additive or synergistic interaction. The protein expressions of TS, FPGS, and RFC1 were significantly associated with IC50 for 5-fluorouracil, but no such association was found for pemetrexed chemosensitivity. The mRNA expressions of RFC1, FPGS and other target and resistance related genes revealed no significant association with pemetrexed sensitivity. In conclusion, pemetrexed is active against gastric cancer cell lines and the pemetrexed/cisplatin combination showed a synergistic or additive interaction, supporting its clinical use in gastric cancer. Drug sensitivity toward pemetrexed could not be predicted by the expressions of TS, RFC1, or FPGS and we suggest that it is determined by interactions between multiple genes.
- 342005
제1저자 강철인 · 교신저자 오명돈
, , , , , , ,
Clinical features and outcome of patients with community-acquired Pseudomonas aeruginosa bacteraemia.Clin Microbiol Infect. 2005;11(5):415-8.
PubMed IF 8.7 감염내과Abstract
Cases of community-acquired Pseudomonas aeruginosa bacteraemia (n = 39) that occurred at a tertiary-care hospital during a 5-year period were analysed retrospectively. The commonest underlying diseases were solid tumour (41%) and haematological malignancy (18%). Most (44%) of the patients were neutropenic, and 39% had septic shock at initial presentation. The 30-day attributable mortality rate was 39%. Two previously healthy patients were identified with fatal P. aeruginosa pneumonia with bacteraemia. P. aeruginosa bacteraemia is a fatal infection that should be considered in the differential diagnosis of patients presenting from the community with rapidly progressive sepsis.
- 332005
제1저자 박영주 · 교신저자 박도준
, , , , , , , ,
p66Shc expression in proliferating thyroid cells is regulated by thyrotropin receptor signaling.Endocrinology. 2005;146(5):2473-80.
PubMed IF 3.8 내분비대사내과Abstract
It is almost unanimously accepted that thyrocyte proliferation is synergistically activated by TSH and insulin/IGF-I. Moreover, it was recently suggested that p66Shc, which is an adaptor molecule of the IGF-I receptor, might play a critical role in this synergistic effect. In this study, we undertook to confirm the role and the mechanism underlying the regulation of p66Shc expression via TSH receptor in thyrocytes. We have found that p66Shc expression is elevated in proliferating human thyroid tissues, including adenomatous goiter, adenoma, Graves' disease, and thyroid cancer, but not in normal thyroid. Among growth factors, TSH increased p66Shc expression both in vivo and in vitro; however, IGF-I, epidermal growth factor, or insulin did not. TSH and Graves' Ig increased the p66Shc expression via the TSH receptor-G(s)-cAMP pathway. However, interestingly, IGF-I or epidermal growth factor increased the tyrosine phosphorylations of p66Shc, and this was enhanced by TSH pretreatment. A similar synergism was observed during the DNA synthesis. When we measured the p66Shc levels induced by individual Igs from 130 patients with Graves' disease, TSH receptor stimulating activity and goiter size showed a weak correlation. We conclude that the expression of p66Shc is regulated by signaling through the TSH receptor in proliferating thyroid cells and that p66Shc appears to be an important mediator of the synergistic effect between TSH and IGF-I with respect to thyrocyte proliferation. Moreover, we suggest that TSH potentiates the regulatory effect of IGF-I on thyrocyte growth, at least in part, by increasing the expression of p66Shc.
- 322005
제1저자 Lee YY · 교신저자 박경수
, , , , , , , , , ,
Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population.Diabet Med. 2005;22(5):569-75.
PubMed IF 3.3 내분비대사내과Abstract
AIMS To investigate any association between Type 2 diabetes mellitus and two single nucleotide polymorphisms (SNPs) in the adiponectin gene, T45G and G276T, in the Korean population.
METHODS We genotyped 427 non-diabetic controls and 493 Type 2 diabetic patients for SNPs T45G and G276T of adiponectin gene, measured plasma adiponectin concentrations, and examined clinical parameters in Koreans.
RESULTS There were no statistically significant differences in allele frequencies of SNPs 45 and 276 comparing control with Type 2 diabetic subjects (T frequency 68.3% vs. 71.6%, P=0.13 for SNP45, G frequency 72.2% vs. 68.9%, P=0.12 for SNP276). The genotype distributions of these SNPs had no association with the risk of Type 2 diabetes and metabolic parameters of insulin resistance. Plasma levels of adiponectin were not statistically different according to T45G and G276T either, in both control and Type 2 diabetic subjects.
CONCLUSION The T45G and G276T of the adiponectin gene may not be an important determinant of Type 2 diabetes or insulin resistance in Korean subjects.
- 312005
제1저자 윤정민 · 교신저자 김영환
, , , , , , ,
Adenovirus-uteroglobin suppresses COX-2 expression via inhibition of NF-kappaB activity in lung cancer cells.Lung Cancer. 2005;48(2):201-9.
PubMed IF 5.3 호흡기내과Abstract
Uteroglobin (UG, Clara cell secretory protein) is a steroid inducible, multifunctional protein that is secreted by the mucosal epithelia. UG has anti-proliferative and anti-metastatic effects in cancer cells. COX-2, which catalyzes the first step in the synthesis of prostanoids, has been shown to be overexpressed in tumors. This study investigated the effect of UG on the inhibition of COX-2 expression in lung cancer cells. The level of the COX-2 protein and its mRNA were decreased by UG, as demonstrated by Western blot and the RT-PCR, respectively. The EIA shows that UG suppressed PGE2 synthesis. Western blot showed that the NF-kappaB nuclear translocation was inhibited by the transduction of UG. In addition, an EMSA demonstrated the inhibition of the NF-kappaB-DNA binding by UG. The luciferase assay showed that UG also inhibited the NF-kappaB-mediated transcription activity. Furthermore, transfection of the lung cancer cell lines with the COX-2 reporter gene constructs demonstrated that the transcription of COX-2 gene was suppressed by UG. These results show that the inhibition of COX-2 expression by UG transduction correlated with the suppression of NF-kappaB activity in the lung cancer cells. This suggests that UG have the possibility for the treatment of lung cancer.
- 302005
제1저자 한세원 · 교신저자 김태유
, , , , , , , , , , , , , , ,
Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib.J Clin Oncol. 2005;23(11):2493-501.
PubMed IF 44.7 혈액종양내과Abstract
PURPOSE This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non-small-cell lung cancer (NSCLC) patients treated with gefitinib.
PATIENTS AND METHODS For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression.
RESULTS Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contrast to 13.7% (10 of 73 patients; 95% CI, 5.8 to 21.6) in patients without mutation (P < .001). Moreover, these 17 patients with EGFR mutation had significantly prolonged TTP (21.7 v 1.8 months; P < .001) and overall survival (30.5 v 6.6 months; P < .001) compared with the remaining 73 patients without mutation. Although no significant correlation was detected between EGFR mutation and expressions of p-Akt or p-Erk, p-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation.
CONCLUSION Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.
- 292005
제1저자 김형관 · 교신저자 손대원
, , , , , ,
Differences in the immediate effects of smoking on left ventricular diastolic function between healthy volunteers and patients with type 2 diabetes mellitus.J Am Soc Echocardiogr. 2005;18(4):320-5.
PubMed IF 8.3 순환기내과Abstract
BACKGROUND In contrast to in-depth studies on the chronic hazardous effects of smoking, the immediate effects of smoking on left ventricular function have not been evaluated in detail.
OBJECTIVES We aimed to assess the hypothesis that smoking a cigarette might have more deleterious immediate impacts on left ventricular function in patients with diabetes mellitus than in healthy volunteers.
METHODS In all, 20 patients with type 2 diabetes mellitus and 25 healthy volunteers were consecutively enrolled. Mitral inflow parameters (peak early and late diastolic velocities, and deceleration time of early diastolic mitral inflow) and mitral annulus velocity parameters (systolic, late, and early diastolic velocity [E']) were obtained together with heart rate and blood pressure before and 5, 15, 30, 45, 60, and 75 minutes after smoking a cigarette.
RESULTS Transient elevations in heart rate and blood pressure were observed after smoking in both groups. In terms of mitral inflow parameters, transient trends toward abnormal relaxation were noted in both groups. For mitral annulus velocity parameters, in contrast to a temporary decrease in E' in healthy volunteers, reduction in E' persisted throughout the study for patients with diabetes. No significant change in peak early diastolic velocity/E' ratio was observed in healthy volunteers; however, a significant increase in peak early diastolic velocity/E' ratio lasted throughout the study period for patients with diabetes. Systolic velocity had no significant change during the study in either group.
CONCLUSIONS Even one cigarette can induce more protracted and more severe left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus than in healthy volunteers. Our results have clinically relevant implications in the current era of increasing recognition of the diabetes epidemic and of the associated cardiovascular risks.
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